T-helper 2 involvement in the pathogenesis of bullous pemphigoid: role of soluble CD30 (sCD30).
Bullous pemphigoid (BP) is an autoimmune blistering skin disease in which autoantibodies are directed against hemidesmosomal proteins of basal keratinocytes. The presence of activated T helper cells in lesions and peripheral blood of BP patients, the eosinophilia, the high levels of serum IgE, eosinophil cationic protein and soluble immune products such as IL-2, sIL-2R, IL-5, soluble CD23 (sCD23) strongly suggest the involvement of a cell-mediated immune reaction in which Th2 lymphocytes could play a pivotal role. To seek evidence to support this hypothesis we evaluated serum levels of IL-4 and sCD30, a specific activation marker of cells able to produce Th2-like cytokines, in 25 patients affected with BP. Serum from both healthy donors and pemphigus vulgaris (PV) patients were used as controls. Our results demonstrated significantly higher levels of IL-4 and sCD30 in patients with BP in relation to both normal individuals (16.6 +/- 7.9 vs 4.5 +/- 2.2 pg/ml, P < 0.0001; 30.3 +/- 10 vs 10.5 +/- 4 U/ml, P < 0.0001) and PV patients (6.2 +/- 4 pg/ml, P < 0.0001; 16 +/- 8.5 U/ml, P < 0.0001). Furthermore, a positive correlation between IL-4 and sCD30 was found (R = 0.85, P < 0.0001). In a subset of seven patients observed after systematic immunosuppressive therapy, we detected a significant reduction in sCD30 serum level (36.9 +/- 7.3 vs 16.3 +/- 6.8 U/ml, P = 0.002), with a parallel improvement in their clinical condition. These results seem to be consistent with the systematic involvement of Th2 lymphocytes in the pathogenesis of BP and suggest a role for sCD30 as a serological marker of disease activity.
De Pitá
O
O
Department of Immunodermatology, Istituto Dermopatico dell' Immacolata, IDI, IRCCS, Rome, Italy.
Frezzolini
A
A
Cianchini
G
G
Ruffelli
M
M
Teofoli
P
P
Puddu
P
P
D000368:Aged; D016022:Case-Control Studies; D005069:Evaluation Studies as Topic; D005260:Female; D006801:Humans; D015847:Interleukin-4 / Q000097:blood*; D017730:Ki-1 Antigen / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010391:Pemphigoid, Bullous / Q000276:immunology*; D012995:Solubility; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018418:Th2 Cells
D017730:Ki-1 Antigen; D015847:Interleukin-4